The present invention relates to a method of producing dicarboxylic acids (e.g., α,ω dicarboxylic acids) by reacting a compound having a terminal COOH (e.g., unsaturated fatty acids such as oleic acid) and containing at least one carbon-carbon double bond with a second generation Grubbs catalyst in the absence of solvent to produce dicarboxylic acids. The method is conducted in an inert atmosphere (e.g., argon, nitrogen).
Aliphatic dicarboxylic acids are important intermediates in the synthesis of biodegradable polymers (Gunatillake, P. A., and R. Adhikari, Eur. Cells & Mater., 5: 1-16 (2003)). Short-chain linear-α,ω-dicarboxylic acids such as suberic acid (C8), azelaic acid (C9), or sebacic acid (C10), which can be derived from fats and oils by chemical oxidation of unsaturated fatty acids, are particularly important building blocks in the synthesis of commercially important materials such as nylons, cosmetics, plasticizers, lubricants, and greases (Johnson, R. W., Fatty Acids in Industry, Marcel Dekker, New York, 1989; Pattison, E. S., Fatty Acids and their Industrial Applications, Marcel Dekker, New York, p. 301 (1968)). It is known that the chain length of the dicarboxylic acid in polymers not only influences polymer properties but also the degradation rate of the polymers. Accordingly, the availability of a variety of α,ω-dicarboxylic acids of varying chain length could potentially lead to new polymeric materials that have better performance properties and are more biodegradable. Research in producing aliphatic α,ω-dicarboxylic acids of carbon chain-length >10 started in the 1970s. Such long-chain α,ω-dicarboxylic acids were produced by either microbial oxidation or microbial fermentation (Atomi, H., et al., J. Ferment. Bioeng., 77: 205-207 (1994)). In the 1980s, several research groups reported that microorganisms, including Candida tropicalis or Candida cloacae, could transform n-alkanes and fatty acids to dicarboxylic acids (Liu, S., et al., Enzyme and Microbiol. Technol., 34: 73-77 (2004); Zu Hua, Y., and R. Hans Juergen, Applied Microbiol. and Biotechnol., 30: 327-331 (1989)). Furthermore, α,ω-diacids of C11 to C18 chain-length are produced in China and unsaturated α,ω-diacids, particularly α,ω-octadecanedioic acid, from vegetable and animal raw materials (Kroha, K., Inform., 15: 568-571 (2004)); using the latter diacid, a series of nylons of both homo- and co-polymers was synthesized (Mao, J., et al., Diacids Made from Renewable Resources and Their Applications in Polymers, Abstract, Biotechnology Posters, 95th AOCS Annual Meeting & Expo, Cincinnati, Ohio (2004)). Although microbial fermentation processes have been used for commercial production of long-chain α,ω-dicarboxylic acids, there are environmental concerns with these processes. Fermentation processes produce aqueous waste containing expired microbial cells, microbial metabolites, and unutilized growth media, which place significant biological demand on water treatment systems. Additionally, the yields of diacids are variable and often poor.
Alternatively, long-chain dicarboxylic acids can be synthesized by chemical approaches. In 1974, there was reported the synthesis of long chain dicarboxylic acids (C18-C26) by the self-metathesis of monounsaturated carboxylic acid esters in the presence of tungsten hexachloride (WCl6) and tetramethyltin (Me4Sn) co-catalysts in chlorobenzene solution; in this manner, monounsaturated fatty esters such as methyl octadec-9-enoate (methyl oleate, 3a, FIG. 2) were converted to dicarboxylate esters with conversions ranging from 50 to 89% and the diesters could be saponified and acidified to give the long-chain dicarboxylic acids (Van Dam, P. B., et al., J. Am. Oil. Chem. Soc., 51:389-391 (1974)). Subsequently, the co-metathesis of methyl oleate with cis-dimethyl-3-hexendioate was carried out using both homogeneous catalysts (WCl6, Me4Sn) and heterogeneous (Re2—Al2O3) catalysts (Kohashi, H., et al., J. Am. Oil. Chem. Soc., 62:549-554 (1985)). Although these synthetic approaches gave high selectivity and high conversions, the catalyst systems used suffered from low catalyst turnover numbers.
In the 1990s, it was demonstrated that homogeneous ruthenium-based catalysts were effective in catalyzing olefin metathesis; moreover, these catalysts, in contrast to the tungsten and rhenium catalysts, often tolerate functionally substituted alkenes (Grubbs, R. H., Handbook of Metathesis, Wiley-Vch, Verlag GmbH & Co. KGaA, Weinheim (2003)). Such ruthenium-based catalysts have been used to prepare α,ω-dicarboxylate esters via metathetic routes. For example, a two-step process was reported using Grubbs catalysts to prepare long-chain unsaturated α,ω-dicarboxylate methyl esters (Warwel, S., et al., Polym. Sci. Part A: Polym. Chem., 39: 1601-1609 (2001)). Cross-metathesis of monounsaturated carboxylic acid methyl esters with ethylene in the presence of the first generation catalyst 1 (FIG. 1) in solution initially gave terminally unsaturated monocarboxylate methyl esters. The resulting terminal monounsaturated esters then underwent self-metathesis in the presence of catalyst 1 to give long-chain α,ω-dicarboxylic acid methyl esters with an overall yield between 38-40% (Warwel, S., et al., Polym. Sci. Part A: Polym. Chem., 39: 1601-1609 (2001); Warwel, S., et al., Ind. Crops & Prod., 20: 301-309 (2004); Warwel, S., et al., Macromol. Chem. Phys., 202: 1114-1121 (2001); Warwel, S., et al., Macromol. Chem. Phys., 202: 849-855 (2001); Warwel, S., et al., Chemosphere, 43: 39-48 (2001)). Self-metathesis of methyl oleate in dichloromethane was reported using the second generation Grubbs catalyst 2 (FIG. 1) and gave the long chain α,ω-dicarboxylic methyl ester 5a (FIG. 2, Eq. 1) in ˜45% conversion (Dinger, M. B., and J. C. Mol, et al., Adv. Synth. Catal., 344: 671-677 (2002)). The self-metathesis of oleic acid in the presence of Cl2(PCy3)2Ru=CH—CH═CPh2 in dichloromethane solution was reported to give 1,18-octadec-9-enedioic acid (5b) and octadec-9-ene (4) in 42% yield (U.S. Pat. No. 5,728,917). However, this process gave low conversion (about 50%) of monounsaturated fatty acids and low yields of dicarboxylic acids. In addition, the reaction was performed in a solvent, dichloromethane, which is an environmental concern.
We have developed an efficient solvent-free self-metathesis process for the conversion of unsaturated hydrocarbons, such as monounsaturated fatty acids, using second generation Grubbs catalysts to afford products such as α,ω-unsaturated dicarboxylic acids and hydrocarbons in very high conversions.